No abstract

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of fractures according to several studies. The underlying mechanisms remain unclear, although small case-control studies indicate poor quality of the cortical bone. We have studied a population-based sample of women aged 75 to 80 years in Gothenburg, randomly invited from the population register. Areal bone mineral density (aBMD) was measured by dual-energy X-ray absorptiometry (Hologic Discovery A), bone microarchitecture by high-resolution peripheral quantitative computed tomography (HR-pQCT; ExtremeCT from Scanco Medical AG), and reference point indentation was performed with Osteoprobe (Active Life Scientific). Women with T2DM (n ¼ 99) had higher aBMD compared to controls (n ¼ 954). Ultradistal tibial and radial trabecular bone volume fraction (þ11% and þ15%, respectively), distal cortical volumetric BMD (þ1.6% and þ1.7%), cortical area (þ11.5% and þ9.3%), and failure load (þ7.7% and þ12.9%) were higher in diabetics than in controls. Cortical porosity was lower (mean AE SD: 1.5% AE 1.1% versus 2.0% AE 1.7%, p ¼ 0.001) in T2DM in the distal radius but not in the ultradistal radius or the tibia. Adjustment for covariates (age, body mass index, glucocorticoid treatment, smoking, physical activity, calcium intake, bone-active drugs) eliminated the differences in aBMD but not in HR-pQCT bone variables. However, bone material strength index (BMSi) by reference point indentation was lower in T2DM (74.6 AE 7.6 versus 78.2 AE 7.5, p < 0.01), also after adjustment, and women with T2DM performed clearly worse in measures of physical function (one leg standing: -26%, 30-s chair-stand test: -7%, timed up and go: þ12%, walking speed: þ8%; p < 0.05-0.001) compared to controls. In conclusion, we observed a more favorable bone microarchitecture but no difference in adjusted aBMD in elderly women with T2DM in the population compared to nondiabetics. Reduced BMSi and impaired physical function may explain the increased fracture risk in T2DM.

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In this paper we investigate error thresholds on dynamic fitness landscapes. We show that there exists both a lower and an upper threshold, representing limits to the copying fidelity of simple replicators. The lower bound can be expressed as a correction term to the error threshold present on a static landscape. The upper error threshold is a new limit that only exists on dynamic fitness landscapes. We also show that for long genomes and/or highly dynamic fitness landscapes there exists a lower bound on the selection pressure required for the effective selection of genomes with superior fitness independent of mutation rates, i.e. there are distinct nontrivial limits to evolutionary parameters in dynamic environments.